期刊
出版社
ELSEVIER
DOI: 10.1016/j.jchromb.2022.123428
关键词
Methylated adenosine; Breast cancer; HILIC-MS/MS; Biomarker; Urine; Plasma
资金
- Natural Science Foundation of Zhejiang Province [LY19B050007]
- National Natural Science Foundation of China [21402172, 22176167]
RNA modifications play essential roles in biological activities and are associated with human diseases, including cancers. This study established a method to quantify six nucleosides in urine and plasma samples, and found altered concentrations of certain nucleosides in breast cancer patients. Furthermore, the ratios of methylated adenosine nucleosides to adenosine in plasma were better at distinguishing breast cancer patients from healthy controls.
RNA modifications have been revealed to be essential in many biological activities, and their disorders are associated with various human diseases, including cancers. 2 ' -O-methyladenosine (A(m)), N-1-methyladenosine (m(1)A), N-6-methyladenosine (m(6)A), N-6,2 '-O-dimethyladenosine (m(6)A(m)) and N-6,N-6-dimethyladenosine (m(2)(6)A) are important adenosine (A) modifications. The noninvasive collection of urine samples and the diverse contents of metabolites in plasma make them favored biofluids for biomarkers discovery. In this work, we established a hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method to quantify these six nucleosides in urine and plasma of healthy controls and breast cancer (BC) patients. The limit of detection (LOD) for A, A(m), m(1)A, m(6)A, m(6)A(m), and m(2)(6)A were 0.0025, 0.01, 0.05, 0.005, 0.005, and 0.005 nM. The results showed that the concentrations of A(m), m(6)A, and m(6)A(m) were increased, whereas m(1)A was decreased in the urine of BC patients compared with the healthy controls. We also found that the level ratios of m(1)A/A, m(6)A/A, and m(6)A(m)/A were all reduced in plasma from BC patients, compared with healthy controls. Interestingly, these ratios of methylated adenosine nucleosides to adenosine in plasma could better discriminate BC patients from healthy controls, compared to the levels of these nucleosides. The present study not only suggests these modified adenosines can act as noninvasive biomarkers of BC but also will contribute to investigating the impacts of RNA methylation on the occurrence and development of BC.
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